Cartilage allograft plug

ABSTRACT

The invention is directed toward a cartilage repair assembly comprising a shaped allograft structure of subchondral bone with an integral overlying cartilage cap which is treated to remove cellular debris and proteoglycans and milled allograft cartilage in a bioabsorbable carrier. The shaped structure is dimensioned to fit in a drilled bore in a cartilage defect area so that either the shaped bone or the cartilage cap engage the side wall of the drilled bore in an interference fit and is in contact with a milled cartilage and biocompatible carrier mixture allowing cell transfer throughout the defect area. A method for inserting the shaped allograft structure into a cartilage defect area is also disclosed.

RELATED APPLICATIONS

There is no related application.

FIELD OF INVENTION

The present invention is generally directed toward an implant and ismore specifically directed toward an allograft implant having acartilage face and bone body which has been treated to remove cellulardebris and proteoglycans and is shaped for an interference fitimplantation in a shoulder or knee joint. The implant is provided withchannels which allow transport of cellular materials throughout theimplant site to stimulate cartilage growth

BACKGROUND OF THE INVENTION

Articular cartilage injury and degeneration present medical problems tothe general population which are constantly addressed by orthopedicsurgeons. Every year in the United States, over 500,000 arthroplastic orjoint repair procedures are performed. These include approximately125,000 total hip and 150,000 total knee arthroplastics and over 41,000open arthroscopic procedures to repair cartilaginous defects of theknee.

In the knee joint, the articular cartilage tissue forms a lining whichfaces the joint cavity on one side and is linked to the subchondral boneplate by a narrow layer of calcified cartilage tissue on the other.Articular cartilage (hyaline cartilage) consists primarily ofextracellular matrix with a sparse population of chondrocytesdistributed throughout the tissue. Articular cartilage is composed ofchondrocytes, type II collagen fibril meshwork, proteoglycans and water.Active chondrocytes are unique in that they have a relatively lowturnover rate and are sparsely distributed within the surroundingmatrix. The collagens give the tissue its form and tensile strength andthe interaction of proteoglycans with water give the tissue itsstiffness to compression, resilience and durability. The hyalinecartilage provides a low friction bearing surface over the bony parts ofthe joint. If the lining becomes worn or damaged resulting in lesions,joint movement may be painful or severely restricted. Whereas damagedbone typically can regenerate successfully, hyaline cartilageregeneration is quite limited because of it's limited regenerative andreparative abilities.

Articular cartilage lesions generally do not heal, or heal onlypartially under certain biological conditions due to the lack of nerves,blood vessels and a lymphatic system. The limited reparativecapabilities of hyaline cartilage usually results in the generation ofrepair tissue that lacks the structure and biomechanical properties ofnormal cartilage. Generally, the healing of the defect results in afibrocartilaginous repair tissue that lacks the structure and biomedicalproperties of hyaline cartilage and degrades over the course of time.Articular cartilage lesions are frequently associated with disabilityand with symptoms such as joint pain, locking phenomena and reduced ordisturbed function. These lesions are difficult to treat because of thedistinctive structure and function of hyaline cartilage. Such lesionsare believed to progress to severe forms of osteoarthritis.Osteoarthritis is the leading cause of disability and impairment inmiddle-aged and older individuals, entailing significant economic,social and psychological costs. Each year, osteoarthritis accounts foras many as 39 million physician visits and more than 500,000hospitalizations. By the year 2020, arthritis is expected to affectalmost 60 million persons in the United States and to limit the activityof 11.6 million persons.

There are many current therapeutic methods being used. None of thesetherapies has resulted in the successful regeneration of hyaline-liketissue that withstands normal joint loading and activity over prolongedperiods. Currently, the techniques most widely utilized clinically forcartilage defects and degeneration are not articular cartilagesubstitution procedures, but rather lavage, arthroscopic debridement,and repair stimulation. The direct transplantation of cells or tissueinto a defect and the replacement of the defect with biologic orsynthetic substitutions presently accounts for only a small percentageof surgical interventions. The optimum surgical goal is to replace thedefects with cartilage-like substitutes so as to provide pain relief,reduce effusions and inflammation, restore function, reduce disabilityand postpone or alleviate the need for prosthetic replacement.

Lavage and arthroscopic debridement involve irrigation of the joint withsolutions of sodium chloride, Ringer or Ringer and lactate. Thetemporary pain relief is believed to result from removing degenerativecartilage debris, proteolytic enzymes and inflammatory mediators. Thesetechniques provide temporary pain relief, but have little or nopotential for further healing.

Repair stimulation is conducted by means of drilling, abrasionarthroplasty or microfracture. Penetration into the subchondral boneinduces bleeding and fibrin clot formation which promotes initialrepair, however, the tissue formed is fibrous in nature and not durable.Pain relief is temporary as the tissue exhibits degeneration, loss ofresilience, stiffness and wear characteristics over time.

The periosteum and perichondrium have been shown to contain mesenchymalprogenitor cells capable of differentiation and proliferation. They havebeen used as grafts in both animal and human models to repair articulardefects. Few patients over 40 years of age obtained good clinicalresults, which most likely reflects the decreasing population ofosteochondral progenitor cells with increasing age. There have also beenproblems with adhesion and stability of the grafts, which result intheir displacement or loss from the repair site.

Transplantation of cells grown in culture provides another method ofintroducing a new cell population into chondral and osteochondraldefects. Carticel® is a commercial process to culture a patient's owncartilage cells for use in the repair of cartilage defects in thefemoral condyle marketed by Genzyme Biosurgery in the United States andEurope. The procedure uses arthroscopy to take a biopsy from a healthy,less loaded area of articular cartilage. Enzymatic digestion of theharvested tissue releases the cells that are sent to a laboratory wherethey are grown for a period ranging from 2-5 weeks. Once cultivated, thecells are injected during a more open and extensive knee procedure intoareas of defective cartilage where it is hoped that they will facilitatethe repair of damaged tissue. An autologous periosteal flap with cambiumlayer is used to seal the transplanted cells in place and act as amechanical barrier. Fibrin glue is used to seal the edges of the flap.This technique preserves the subchondral bone plate and has reported ahigh success rate. Proponents of this procedure report that it producessatisfactory results, including the ability to return to demandingphysical activities, in more than 90% of patients and that biopsyspecimens of the tissue in the graft sites show hyaline-like cartilagerepair. More work is needed to assess the function and durability of thenew tissue and determine whether it improves joint function and delaysor prevents joint degeneration. As with the perichondrial graft,patient/donor age may compromise the success of this procedure aschondrocyte population decreases with increasing age. Disadvantages tothis procedure include the need for two separate surgical procedures,potential damage to surrounding cartilage when the periosteal patch issutured in place, the requirement of demanding microsurgical techniques,and the expensive cost of the procedure which is currently not coveredby insurance.

Osteochondral transplantation or mosaicplasty involves excising allinjured or unstable tissue from the articular defect and creatingcylindrical holes in the base of the defect and underlying bone. Theseholes are filled with autologous cylindrical plugs of healthy cartilageand bone in a mosaic fashion. The osteochondral plugs are harvested froma lower weight-bearing area of lesser importance in the same joint. Thistechnique, shown in Prior Art FIG. 2, can be performed as arthroscopicor open procedures. Reports of results of osteochondral plug autograftsin a small numbers of patients indicate that they decrease pain andimprove joint function, however, long-term results have not beenreported. Factors that can compromise the results include donor sitemorbidity, effects of joint incongruity on the opposing surface of thedonor site, damage to the chondrocytes at the articular margins of thedonor and recipient sites during preparation and implantation, andcollapse or settling of the graft over time. The limited availability ofsites for harvest of osteochondral autografts restricts the use of thisapproach to treatment of relatively small articular defects and thehealing of the chondral portion of the autograft to the adjacentarticular cartilage remains a concern.

Transplantation of large allografts of bone and overlying articularcartilage is another treatment option that involves a greater area thanis suitable for autologous cylindrical plugs, as well as for anon-contained defect. The advantages of osteochondral allografts are thepotential to restore the anatomic contour of the joint, lack ofmorbidity related to graft harvesting, greater availability thanautografts and the ability to prepare allografts in any size toreconstruct large defects. Clinical experience with fresh and frozenosteochondral allografts shows that these grafts can decrease jointpain, and that the osseous portion of an allograft can heal to the hostbone and the chondral portion can function as an articular surface.Drawbacks associated with this methodology in the clinical situationinclude the scarcity of fresh donor material and problems connected withthe handling and storage of frozen tissue. Fresh allografts carry therisk of immune response or disease transmission. MusculoskeletalTransplant Foundation (MTF) has preserved fresh allografts in a mediathat maintains a cell viability of 50% for 35 days for use as implants.Frozen allografts lack cell viability and have shown a decreased amountof proteoglycan content which contribute to deterioration of the tissue.

A number of United States Patents have been specifically directedtowards bone plugs which are implanted into a bone defect. Examples ofsuch bone plugs are U.S. Pat. No. 4,950,296 issued Aug. 21, 1990 whichdiscloses a bone graft device comprising a cortical shell having aselected outer shape and a cavity formed therein for receiving acancerous plug, and a cancellous plug fitted into the cavity in a mannerto expose at least one surface; U.S. Pat. No. 6,039,762 issued Mar. 21,2000 having a cylindrical shell with an interior body of deactivatedbone material and U.S. Pat. No. 6,398,811 issued Jun. 4, 2002 directedtoward a bone spacer which has a cylindrical cortical bone plug with aninternal throughgoing bore designed to hold a reinforcing member. U.S.Pat. No. 6,383,211 issued May 7, 2002 discloses an invertebral implanthaving a substantially cylindrical body with a throughgoing boredimensioned to receive bone growth materials.

U.S. Pat. No. 6,379,385 issued Apr. 30, 2002 discloses an implant basebody of spongious bone material into which a load carrying supportelement is embedded. The support element can take the shape of adiagonal cross or a plurality of cylindrical pins. See also, U.S. Pat.No. 6,294,187 issued Sep. 25, 2001 which is directed to a load bearingosteoimplant made of compressed bone particles in the form of acylinder. The cylinder is provided with a plurality of throughgoingbores to promote blood flow through the osteoimplant or to hold ademineralized bone and glycerol paste mixture. U.S. Pat. No. 6,096,081issued Aug. 1, 2000 shows a bone dowel with a cortical end cap or capsat both ends, a brittle cancerous body and a throughgoing bore.

A number of patents in the prior art show the use of bone putty, pastesor gels to fill bone defects. U.S. Pat. No. 5,290,558 issued Mar. 1,1994 discloses a flowable demineralized bone powder composition using anosteogenic bone powder with large particle size ranging from about 0.1to about 1.2 cm. mixed with a low molecular weight polyhydroxy compoundpossessing from 2 to about 18 carbons including a number of classes ofdifferent compounds such as monosaccharides, disaccharides, waterdispersible oligosaccharides and polysaccharides.

A bone gel is disclosed in the U.S. Pat. No. 5,073,373 issued Dec. 17,1991. Bone lamellae in the shape of threads or filaments retaining lowmolecular weight glycerol carrier are disclosed in U.S. Pat. No.5,314,476 issued May 24, 1994 and U.S. Pat. No. 5,507,813 issued Apr.16, 1996 and the tissue forms described in these patents are knowncommercially as the GRAFTON® Putty and Flex, respectively.

U.S. Pat. No. 5,356,629 issued Oct. 18, 1994 discloses making a rigidgel in the nature of a bone cement to fill defects in bone by mixingbiocompatible particles, preferably polymethylmethacrylate coated withpolyhydroxyethylmethacrylate in a matrix selected from a group whichlists hyaluronic acid to obtain a molded semi-solid mass which can besuitably worked for implantation into bone. The hyaluronic acid can alsobe utilized in monomeric form or in polymeric form preferably having amolecular weight not greater than about one million Daltons. It is notedthat the nonbioabsorbable material which can be used to form thebiocompatible particles can be derived from xenograft bone, homologousbone, autogenous bone as well as other materials. The bioactivesubstance can also be an osteogenic agent such as demineralized bonepowder morselized cancerous bone, aspirated bone marrow and otherautogenous bone sources. The average size of the particles employed ispreferably about 0.1 to about 3.0 mm, more preferably about 0.2 to about1.5 mm, and most preferably about 0.3 to about 1.0 mm. It isinferentially mentioned but not taught that particles having averagesizes of about 7,000 to 8,000 microns, or even as small as about 100 to700 microns can be used.

U.S. Pat. No. 4,172,128 issued Oct. 23, 1979 discloses a demineralizedbone material mixed with a carrier to reconstruct tooth or bone materialby adding a mucopolysaccharide to a mineralized bone colloidal material.The composition is formed from a demineralized coarsely ground bonematerial, which may be derived from human bones and teeth, dissolved ina solvent forming a colloidal solution to which is added aphysiologically inert polyhydroxy compound such as mucopolysaccharide orpolyuronic acid in an amount which causes orientation when hydrogen ionsor polyvalent metal ions are added to form a gel. The gel will beflowable at elevated temperatures above 35° C. and will solidify whenbrought down to body temperature. Example 25 of the patent notes thatmucopolysaccharides produce pronounced ionotropic effects and thathyaluronic acid is particularly responsible for spatial cross-linking

U.S. Pat. No. 6,030,635 issued Feb. 29, 2000 and U.S. Pat. No. 6,437,018issued Aug. 20, 2002 are directed toward a malleable bone putty and aflowable gel composition for application to a bone defect site topromote new bone growth at the site which utilize a new bone growthinducing compound of demineralized lyophilized allograft bone powder.The bone powder has a particle size ranging from about 100 to about 850microns and is mixed in a high molecular weight hydrogel carrier whichcontains a sodium phosphate saline buffer.

The use of implants for cartilage defects is much more limited. Asidefrom the fresh allograft implants and autologous implants, U.S. Pat. No.6,110,209 issued Nov. 5, 1998 shows the use an autologous articularcartilage cancellous bone paste to fill arthritic defects. The surgicaltechnique is arthroscopic and includes debriding (shaving away loose orfragmented articular cartilage), followed by morselizing the base of thearthritic defect with an awl until bleeding occurs. An osteochondralgraft is then harvested from the inner rim of the intercondylar notchusing a trephine. The graft is then morselized in a bone graft crusher,mixing the articular cartilage with the cancerous bone. The paste isthen pushed into the defect and secured by the adhesive properties ofthe bleeding bone. The paste can also be mixed with a cartilagestimulating factor, a plurality of cells, or a biological glue. Allpatients are kept non-weight bearing for four weeks and used acontinuous passive motion machine for six hours each night. Histologicappearance of the biopsies have mainly shown a mixture of fibrocartilagewith hyaline cartilage. Concerns associated with this method are harvestsite morbidity and availability, similar to the mosaicplasty method.

U.S. Pat. No. 6,379,367 issued Apr. 30, 2002 discloses a plug with abase membrane, a control plug, and a top membrane which overlies thesurface of the cartilage covering the defective area of the joint.

SUMMARY OF THE INVENTION

A cartilage allograft construct assembly comprising a plug with asubchondral bone base and cartilage cap for replacing of articularcartilage defects is used together with a milled cartilage in abiocompatible carrier forming a paste or gel which is added to the plugor placed in a bore which has been cut into the patient to remove thelesion defect area. Additives may be applied to the cartilage mixture inorder to increase chondrocyte migration and proliferation. Eachallograft construct can support the addition of a variety ofchondrogenic stimulating factors including, but not limited to growthfactors (FGF-2, FGF-5, IGF-1, TGF-β, BMP-2, BMP-7, PDGF, VEGF), humanallogenic or autologous chondrocytes, human allogenic or autologous bonemarrow cells, stem cells, demineralized bone matrix, insulin,insulin-like growth factor-1, transforming growth factor-B,interleukin-1 receptor antagonist, hepatocyte growth factor,platelet-derived growth factor, Indian hedgehog and parathyroidhormone-related peptide or bioactive glue.

It is an object of the invention to provide an allograft implant forjoints which provides pain relief, restores normal function and willpostpone or alleviate the need for prosthetic replacement.

It is also an object of the invention to provide a cartilage repairimplant which is easily placed in a defect area by the surgeon using anarthroscopic, minimally invasive technique.

It is still another object of the invention to provide an allograftimplant which has load bearing capabilities.

It is further an object of the invention to provide an allograft implantprocedure which is applicable for both partial and full thicknesslesions.

It is yet another object of the invention to provide an allograftimplant which facilitates growth of hyaline cartilage.

It is an additional object of the invention to provide implant plugstogether with paste and gel formulations that satisfy surgicalrequirements and are made from available allograft tissue, some of whichwould otherwise be considered waste and thrown away.

These and other objects, advantages, and novel features of the presentinvention will become apparent when considered with the teachingscontained in the detailed disclosure along with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the anatomy of a knee joint;

FIG. 2 shows a schematic mosaicplasty as known in the prior art; and

FIG. 3 shows a schematic perspective view of an interference fitcylindrical allograft osteochondral plug assembly in a defect site;

FIG. 4 shows a perspective view of the osteochondral plug used in FIG.3;

FIG. 5 shows a perspective view of a cylindrical interference fitallograft osteochondral plug assembly having throughgoing bores;

FIG. 6 shows a perspective view of the osteochondral plug used in FIG.5;

FIG. 7 shows a schematic perspective view of another embodiment of amushroom shaped allograft osteochondral assembly in a defect site;

FIG. 8 shows a perspective view of the mushroom shaped osteochondralplug used in FIG. 7; and

FIG. 9 shows a perspective view of an osteochondral plug with outsidelongitudinal channels.

DESCRIPTION OF THE INVENTION

The term “tissue” is used in the general sense herein to mean anytransplantable or implantable tissue, the survivability of which isimproved by the methods described herein upon implantation. Inparticular, the overall durability and longevity of the implant areimproved, and host-immune system mediated responses, are substantiallyeliminated.

The terms “transplant” and “implant” are used interchangably to refer totissue, material or cells (xenogeneic or allogeneic) which may beintroduced into the body of a patient to replace or supplement thestructure or function of the endogenous tissue.

The terms “autologous” and “autograft” refer to tissue or cells whichoriginate with or are derived from the recipient, whereas the terms“allogeneic” and “allograft” refer to cells and tissue which originatewith or are derived from a donor of the same species as the recipient.The terms “xenogeneic” and “xenograft” refer to cells or tissue whichoriginates with or are derived from a species other than that of therecipient.

The term “gel” refers to a formable mixture of minced or milledpretreated allograft cartilage in a biocomposite carrier having aviscosity which is less than and is less rigid than a mixture of mincedor milled pretreated allograft cartilage in a biocompatible carrierreferred to by the terms “putty” or “paste” and contains less cartilageby weight than putty or paste.

The present invention is directed towards a cartilage repair assemblyand method of treatment. The preferred embodiment and best mode of theinvention is shown in FIGS. 5 and 6. In the production of the invention,an allograft plug with a cartilage cap and hyaline cartilage are treatedto remove cellular material, chondrocytes and pluripotent mesenchymalcells and proteoglycans, freezing same −20° C. to −80° C., andlyophilized reducing its water content.

In the treatment for cell and proteoglycan extraction the allograftcartilage and plugs which were previously harvested from a donor weresoaked in hyaluronidase (type IV-s, 3 mg/mL), trypsin (0.25% inmonodibasic buffer 3 ml) and the samples were placed in a test tube for18 hours at 37° C. with sonication. It was found that sonication is nota necessary requirement and the times of soaking vary with concentrationof hyaluronidase and trypsin and can be as little as 2 hours. The plugsamples were decalcified, washed w/DI water and placed in a 50%/50%chloroform/methanol solution for 72 hours to remove cellular debris andsterilize. The above method has been previously used on human tissue andis set forth in the Journal of Rheumatology, 12:4, 1985 by GustVerbruggen et al titled Repair Function in Organ Cultured HumanCartilage Replacement of Enzymatically Removed Proteoglycans DuringLongterm Organ Culture. After repeated washes with sterile DI water, thehydrated plug samples and cartilage were frozen at −70° C. andlyophilized to reduce the water content within the range of about 0.1%to about 8.0%. In an alternative usage, the plug samples and cartilagewere frozen after processing.

The osteochondral plug 20 which has been treated as noted above isplaced in a bore or core 60 which has been cut in the lesion area of thebone 100 of a patient with the upper surface 25 of the cartilage cap 24being slightly proud or substantially flush with the surface of theoriginal cartilage 102 remaining at the area being treated. The plug 20has a subchondral bone portion 22 and an overlying integral cartilagecap 24. The length of the osteochondral plug 20 can be the same as thedepth of the bore 60 or less than the depth of the bore 60. If the plug20 is the same length, the base of the plug implant is supported and thearticular cartilage cap 24 is level with the articular cartilage 102. Ifthe plug is of a lesser length, the base of the plug implant is notsupported but support is provided by the wall of the bore 60 orrespective cut out area as the plug is interference fit within the boreor cut out area with the cap being slightly proud or flush with thearticular cartilage 102 depending on the surgeon's preference. With suchload bearing support the graft surface is not damaged by weight orbearing loads which can cause micromotion interfering with the graftinterface producing fibrous tissue interfaces and subchondral cysts.

As shown in FIGS. 3 and 5 the respective plug 20, 30 has an interferencefit within bore 60. The osteochondral plug, which is generally referredto as a plug in the present description is also envisioned as havingvarious shapes namely; a cylindrical shape 20, 30 as shown in FIGS. 3-6,a mushroom shape 40 as shown in FIGS. 7 and 8, and a channeled orgrooved shape 50 as shown in FIG. 9.

The preferred embodiment is shown in FIGS. 5 and 6 and has a cylindricalbody 30 with a subchondral bone portion 32 and an overlying cartilagecap 34. A plurality of throughgoing bores 36 are drilled through thebone portion 32 and cap 34 to allow cell migration from a cartilagemixture which has been placed in the bore to promote cartilage growth.The cartilage mixture is more fully described later on in thedescription of the invention.

Another embodiment is a mushroom shaped configuration 40 as is shown inFIGS. 7 and 8 which has a cylindrical subchondral bone portion 42 and anoverlying larger diameter cartilage cap 44. The cap 44 is larger indiameter than the body 42 and the periphery 47 of the cap extends pastthe cylindrical wall 43 of the body. If the cap 44 is the same size asthe bore 60 then the body 42 has a length which will engage the floor ofthe bore 60 so that the cap 44 upper cartilage surface 45 is flush withthe upper surface of the surrounding cartilage area 102. Alternately, asecond stepped cut 61 may be made in the cartilage surface area down tothe depth of the bottom of the cartilage layer which will support thebase or lower extending surface 46 of the cap cartilage so that it isflush with the surrounding cartilage area 102 with the lower smallerdiameter of the bore 62 being substantially the same as the diameter ofthe subchondral bone portion with the plug being held therein in aninterference fit.

As shown in FIG. 9 the exterior surface of the implant 50 may be formedwith grooves or channels 52 which can run longitudinally along theoutside surface of the implant or alternatively just along the surfaceof the subchondral bone portion 22, 32, 42 ending at the bottom surfaceof the cartilage cap 24, 34, 44 overlying same. This variation of FIG. 9also has an interference fit with the wall of the bore 62.

In operation the lesion or defect is removed by cutting a bore 60 orremoving a lesion in the implant area 100 and filling the bore 60 or cutaway area with a desired amount of a milled cartilage mixture and abiological carrier such as sodium hyaluronate, hyaluronic acid and itsderivatives, gelatin, collagen, chitosan, alginate, buffered PBS,Dextran, or polymers and one or more additives namely chondrogenicstimulating factors including, but not limited to growth factors (FGF-2,FGF-5, IGF-1, TGF-β, BMP-2, BMP-7, PDGF, VEGF), human allogenic orautologous chondrocytes, human allogenic cells, human allogenic orautologous bone marrow cells, human allogenic or autologous stem cells,demineralized bone matrix, insulin, insulin-like growth factor-1,interleukin-1 receptor antagonist, hepatocyte growth factor,platelet-derived growth factor, Indian hedgehog and parathyroidhormone-related peptide. Depending upon the weight of the milledcartilage as noted in Examples 2 and 3 below, the mixture will have theconsistency of a paste or gel. The plug 20 is then placed in the bore orcut away area in an interface fit with the surrounding walls.

Suitable organic glue material can be used to keep the implant fixed inplace in the implant area. Suitable organic glue material can be foundcommercially, such as for example; TISSEEL® or TISSUCOL.® (fibrin basedadhesive; Immuno AG, Austria), Adhesive Protein (Sigma Chemical, USA),Dow Corning Medical Adhesive B (Dow Corning, USA), fibrinogen thrombin,elastin, collagen, casein, albumin, keratin and the like.

EXAMPLE 1

A non-viable or decellularized osteochondral plug consisting of asubchondral bone base and overlying cartilage cap was treated with asolution or variety of solutions to remove the cellular debris as wellas the proteoglycans as noted in the treatment described above. It isbelieved that this removal provides signaling to stimulate thesurrounding chondrocytes to proliferate and form new proteoglycans andother factors producing new matrix. The diameter or diagonal of the plugranges from 1 mm to 30 mm but is preferably 4 mm to 10 mm which is smallenough to fit through the endoscopic cannula, but large enough tominimize the number of plugs needed to fill large defects. This sizeprovides good results at the recipient site and provides a moreconfluent hyaline surface. The thickness of subchondral bone can bemodified to match the anatomy of the patient so that the surfacecartilage of the plug will be even with and follow the surface contourof the surface cartilage of the host tissue. The treated plug alsocreates a more porous matrix, which allows more cells to enter. The plugand minced hyaline cartilage can be stored frozen or freeze dried andsupport any of the mentioned chondrogenic stimulating factors. The plugcan be inserted arthroscopically similar to the mosaicplasty procedureor through an open incision. The plug and cartilage material can be madein various dimensions depending on the size of the defect being treated.

This design uses the allograft cartilage putty or gel as noted below ina prepackaged amount to provide cartilage cell growth for theosteochondral plug. The putty or gel enhances the tissue integrationbetween the plug and host tissue.

The base of the bore or cut away area is provided with a matrix ofminced cartilage putty consisting of minced or milled allograftcartilage which has been lyophilized so that its water content rangesfrom 0.1% to 8.0% ranging from 25% to 50% by weight, mixed with acarrier of sodium hyaluronate solution (HA) (molecular weight rangingfrom 7.0×10⁵ to 1.2×10⁶) or any other bioabsorbable carrier such ashyaluronic acid and its derivatives, gelatin, collagen, chitosan,alginate, buffered PBS, Dextran, or polymers, the carrier ranging fromranging from 75% to 50% by weight. The cartilage is milled to a sizeranging up to 1 mm.

In gel form, the minced cartilage has been lyophilized so that its watercontent ranges from 0.1% to 8.0%, ranging from 15% to 30% by weight andthe carrier ranges from 85% to 70% by weight. The particle size of thecartilage when milled is less than or equal to 1 mm dry. The cartilagepieces can be processed to varying particle sizes and the HA or othercarrier can have different viscosities depending on the desiredconsistency of the putty or gel. This cartilage matrix can be depositedinto the cartilage defect arthroscopically and fit into the defect whereit is held in place by the implant which is placed over it as a cap.

Cells which have been grown outside the patient are inserted by syringeinto the matrix before, during or after deposit of the cartilage matrixinto the defect area. Such cells include allogenic or autologous, bonemarrow cells, stem cells and chondrocyte cells. The cellular density ofthe cells preferably ranges from 1.0×10⁸ to 5.0×10⁸ or from about 100million to about 500 million cells per cc of putty or gel mixture. Thiscomposite material can be injected into the cartilage defectarthroscopically as previously noted. This matrix can support thepreviously mentioned chondrogenic stimulating factors.

The operation of placing the cartilage defect assembly in a cartilagedefect, comprises (a) drilling a cylindrical hole in a patient at a siteof a cartilage defect to remove the diseased area of cartilage; (b)placing a mixture of milled allograft cartilage in a bioabsorbablecarrier in the drilled cylindrical hole; and ©) placing the pretreatedimplant in the bore over the mixture of the inserted milled allograftcartilage in a bioabsorbable carrier in interference with the wall ofthe bore to contain the mixture in the cylindrical hole for apredetermined period of time to promote cartilage growth at the defectsite.

When using the mushroom shaped embodiment of FIGS. 7 and 8 a secondlarger diameter bore is cut into the bone around the first bore and thecartilage layer is removed to present a stepped bore forming a seat uponwhich the lower surface of the overlying portion of the cartilage cap isseated.

The principles, preferred embodiments and modes of operation of thepresent invention have been described in the foregoing specification.However, the invention should not be construed as limited to theparticular embodiments which have been described above. Instead, theembodiments described here should be regarded as illustrative ratherthan restrictive. Variations and changes may be made by others withoutdeparting from the scope of the present invention as defined by thefollowing claims.

1. A method of placing a preshaped allograft plug assembly in acartilage defect, said assembly comprising a subchondral bone and anoverlying cartilage cap which as been treated to remove cellular debrisand proteoglycans and milled cartilage in a carrier comprising the stepsof: (a) cutting a first cylindrical bore in a patient at a site of acartilage defect area to remove the cartilage defect; (b) cutting asecond cylindrical bore to having a diameter greater than the firstcylindrical bore a depth which is substantially the same as the depth ofa cartilage layer in the defect area to form a stepped bore; (c) placinga mixture of milled cartilage in a bioabsorbable carrier in the formedhole; and (d) placing a preshaped allograft osteochondral plug having across section which engages the walls defining said hole allowing thestructure to be placed in an interference fit within said stepped borewith the surface of the cartilage cap being substantially flush withsurrounding cartilage.
 2. The method of claim 1 wherein the firstcylindrical bore and the second cylindrical bore have the same axis.